Allelic Frequency of DPYD Genetic Variants in Patients With Cancer in Spain: The PhotoDPYD Study

• Published in: The oncologist (Dayton, Ohio) Vol. 28; no. 5; pp. e304 - e308
• Main Authors: Miarons, Marta, Manzaneque Gordón, Alba, Riera, Pau, Gutiérrez Nicolás, Fernando
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 01-05-2023
• Subjects: Brief Communication; Cancer; Cancer patients; Cross-Sectional Studies; Dihydrouracil Dehydrogenase (NADP) - genetics; Drug therapy; Fluorouracil; Genetic aspects; Genetic variation; Genotype; Health aspects; Humans; Neoplasms - epidemiology; Neoplasms - genetics; Oncology, Experimental; Polymorphism, Genetic; Spain - epidemiology; Spain
• ISSN: 1083-7159; 1549-490X
• DOI: 10.1093/oncolo/oyad077

Abstract
Introduction
Identifying polymorphisms in the dihydropyrimidine dehydrogenase (DPYD) gene is gaining importance to be able to predict fluoropyrimidine-associated toxicity. The aim of this project was to describe the frequency of the DPYD variants DPYD*2A (rs3918290); c.1679T>G (rs55886062); c.2846A>T (rs67376798) and c.1129-5923C>G (rs75017182; HapB3) in the Spanish oncological patients.
Material and Methods
Cross-sectional and multicentric study (PhotoDPYD study) conducted in hospitals located in Spain designed to register the frequency of the most relevant DPYD genetic variants in oncological patients. All oncological patients with DPYD genotype were recruited in the participant hospitals. The measures determined where the presence or not of the 4 DPYD previously described variants.
Results
Blood samples from 8054 patients with cancer from 40 different hospitals were used to determine the prevalence of the 4 variants located in the DPYD gene. The frequency of carriers of one defective DPYD variant was 4.9%. The most frequently identified variant was c.1129-5923C>G (rs75017182) (HapB3), in 2.9%, followed by c.2846A>T (rs67376798) in 1.4%, c.1905 + 1G>A (rs3918290, DPYD*2A) in 0.7% and c.1679T>G (rs55886062) in 0.2% of the patients. Only 7 patients (0.08%) were carrying the c.1129-5923C>G (rs75017182) (HapB3) variant, 3 (0.04%) the c.1905 + 1G>A (rs3918290, DPYD*2A) and one (0.01%) the DPYD c.2846A>T (rs67376798, p.D949V) variant in homozygosis. Moreover, 0.07% were compound heterozygous patients, 3 carrying the DPYD variants DPYD*2A + c.2846A>T, 2 the DPYD c.1129-5923C>G + c.2846A>T and one the DPYD*2A + c.1129-5923C>G variants.
Conclusions
Our results demonstrate the relatively high frequency of DPYD genetic variants in the Spanish patient with cancer population, which highlights the relevance of their determination before initiating a fluoropirimidine-containing regimen.
This article describes the frequency of certain DPYD variants in a population of Spanish patients with cancer, with a goal of creating a national registry.